a. Field of the Invention:
This invention relates to a carbonaceous adsorbent to be used for the removal of a pyrogen dissolved in water. It also relates to a method for the removal of endotoxin with the carbonaceous adsorbent in the production of pure water from deionized water resulting from the treatment with ion-exchange resins.
b. Description of the Prior Art:
The "pyrogen" is the generic term applied to all substances which, even in an extremely small amount, cause abnormal elevation of body temperatures of homothermal animals. If a pyrogen finds its way into the blood in a human body as by intravenous injection of a medicine, it causes a violent exothermic reaction independently of the principal action of the medicine. In an extreme case, this exothermic reaction could result in fatal shock.
The pyrogenic toxin consists mainly of the bacterial endotoxin which is a compound lipopolysaccharide occurring as the cell membrane component of gram negative bacteria. The pharmacopoeia in numerous countries prohibit solutions for injection from containing pyrogens as well as microorganisms. The integration of semiconductor elements has advanced to a point where the so-called superpure water obtained by enhancing the purity of normally pure water ultimately to suit production of such semiconductor elements is now required to meet the exacting standard that the number of live microorganisms, the source of pyrogen, should not exceed 0.02/ml.
Production of pure water containing no pyrogen is generally effected by following the operation of distillation defined by the Pharmacopoeia for the purification of water. The pure water obtained by just one round of the distillation, more often than not, gives a positive result in the Limulus test (the test resorting to the gelling reaction of the limulus amberbocyte lysate with endotoxin).
Heretofore, as means of removing pyrogenic substances, the treatment using powdered granulated activated carbon and the treatment using a varying species of ion-exchange resin have been tried. These treatments, however, often experience leaks of liquids under treatment owing to variation of load of pyrogenic substance and cannot be expected to give a stable effect. Thus, as disclosed in Japanese Patent No. 989,058 titled "Method for obtaining refined sugar solution containing no pyrogenic substance" and Japanese Patent No. 738,632 titled "Method for obtaining aqueous solution for injection containing neither pyrogen nor microorganism by treatment of filtration", for example, the membrane separation method using a filtration membrane has come to find widespread acceptance.
Generally, the membrane separation method, instead of being independently used, is incorporated as one element in the extremely expensive system for the production of superpure water. To be specific, this is a method which comprises passing town water containing various ions and organic substances as well as pyrogens in large amounts through activated carbon and/or ion-exchange resin, storing the treated water, and forwarding the water for further treatments through an ultraviolet light sterilizer, a regeneration type mixed-bed type ion-exchange resin column, and a filtration membrane such as an ultrafiltration membrane or a reverse-osmosis membrane. Microorganisms by nature possess a multiplying property. The microorganisms in the water under treatment, even after sterilization of the water, are captured within the system, particularly on the surface of a filtration membrane. In consequence of the growth of the number of killed microorganisms, the concentration of endotoxin continues to increase possibly to the extent of inducing early clogging of the membrane and constituting one factor for the unexpected impairment of the membrane quality.
It is known that once the pyrogen-free water obtained as described above is released from the germ-free condition, it is highly susceptible to micro-organic contamination and is liable to suffer quick formation of endotoxin. In the circumstances, the desirability of developing a medicine, a special adsorbent, or other similar means capable of easily and effectively producing pyrogen-free water has been finding enthusiastic recognition. Various attempts are being made in search of a method capable of effectively removing pyrogens from water by adsorption. In the case of ion-exchange resin, synthetic adsorbent, and various species of activated carbon, for example, porous ion-exchange resins (produced by Rohm and Haas Co. and marketed under registered trademark designations of "Amberlite" 200 and IRA-938) have been demonstrated to produce some effect and synthetic adsorbents such as, for example, Amberlite XAD, and activated carbons have been reported as effective, if not perfectly, in the Journal of Chemical Society of Japan, No. 8, pp. 1547-1553 (1973).